Ester conjugates, sulfate

Figure 2.8 Summary of behavior of phenolic acid esters and free forms in the GIT and the liver. 5-O-CQA, 5-O-caffeoylquinic acid 5-O-FAAF, 5-O-feruloyl-L-arabinofura-nose C, conjugate (sulfate, glucuronide or methyl) CA, caffeic acid FA, ferulic acid FA-FA, dimer of ferulic acid FA-oligosac., ferulic acid esterified to an oligosaccharide FA-Xy, ferulic acid esterified to xylan R, alkyl group.

Although it has been stated that only phenols are conjugated with sulfuric acid,1 three urinary steroid sulfate esters (androsterone sulfate, dehydro-epi-androsterone sulfate, and A 6-aZZo-pregnene-3(/3)-ol-20-one sulfate) have been isolated in which the sulfuric acid is esterified by an alcoholic hydroxyl group.111 It is true that no alcohol administered to... 

Figure 7. Thermospray LC/MS spectrum of a urinary metabolite of SK F 86466, the sulfate ester conjugate.

Table II. Examples of NMR usage in identification of sulfate ester conjugates values in parentheses are for the corresponding OH compound.

Some of the dose does remain on the foil and adhesive. The main (60% of dose) urinary component was identified as the sulfate ester conjugate of 2-ethyl-4-hydroxy-6-methylaniline. In another occlusive study, CGA-73102, C-phenyl-(0-n-butyl-0 -(2,2-dimethyl-2, S-dihydrobenzofurane-I-yD-N.N -dimethyl-N.N -thiodicarbamate) was done to include results on tissue retention 72 hours after dosing (Table III). 

Although addition of acid or base is common practice in FAB MS, one must consider the stability of the analyte in overly acidic or basic solutions. For example, add could promote hydrolysis of glucuronide or sulfate ester conjugates. The resulting analysis would be erroneous owing to the detection of hydrolysis products rather than the spectrum of the intact conjugate. 

Substrates for the sulfotransferases include such varied compounds as primary and secondary alcohols, hydroxysteroids, phenols, organic hydroxylamines, and amines. As is the case with formation of glutathione and glucuronide conjugates, the formation of a sulfate ester usually renders a substance more polar and more readily excreted. Several reviews on the multiple forms of sulfotransferases and their specificities and properties are available (133-135). 

Toad bufadienolides occur not only by themselves but also in a conjugated form, sulfates, dicarboxylic esters and amino acid-dicarboxylic acid esters have all been reported (Steyn and van Heerden 1998). Because of the activity of the bufadienolides in inhibiting active monovalent cation transporters, it is suggested that these compounds have a role in maintaining sodium homeostasis in toads that migrate between fresh and salt water environments (Flier, I idwards, Daly and Myers 1980). 

A number of enzymes known as sulfuric ester hydrolases (EC 3.1.6) are able to hydrolyze sulfuric acid esters. They comprise arylsulfatase (sulfatase, EC 3.1.6.1), steryl-sulfatase (steroid sulfatase, steryl-sulfate sulfohydrolase, arylsulfatase C, EC 3.1.6.2), choline-sulfatase (choline-sulfate sulfohydrolase, EC 3.1.6.6), and monomethyl-sulfatase (EC 3.1.6.16). Whereas mono-methyl-sulfatase is highly specific and does not act on higher homologues, arylsulfatase has a broad substrate specificity and is of particular significance in the hydrolysis of sulfate conjugates of phenols, be they endogenous compounds, drugs, or their metabolites [167-169],... 

The biosynthesis of sulfate esters with the help of phosphoadenosine phosphosulfate (PAPS), the active sulfate , (see p. 110) and amide formation with glycine and glutamine also play a role in conjugation. For example, benzoic acid is conjugated with glycine to form the more soluble and less toxic hippuric acid (N-benzoylglycine see p. 324). 

It is supposed that, once fermentation products have crossed the intestinal barrier, they reach the liver through the portal vein, where they are further metabolized by dehydroxylation, methylation or conjugation to sulfate esters or glucuronides as it has been shown for other flavonoids [59]. 

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